Lecture 3.5: Citrate Cycle

The citrate cycle occurs in the _____ ______

Mitochondria matrix

What are the other names for the citrate cycle

Cirtic acid cycle (CAC), Krebs cycle, tricarboxylic acid cycle (TCA)

How many electrons are captured per Acetyl-CoA

4 pairs of electrons (8 electrons)

What is the fuel for the citrate cycle

Acetyl-CoA

What is the exhaust of the CAC

CO₂

How many FADH are created and how many electrons come from it

1 FADH & 2 electrons

How many NADH are created and how many electrons come from it

3 NADH & 6 electrons

How many steps are in the CAC

8 enzyme-catalyzed reactions

(T/F) Oxygen is an aerobic pathway

False — the citrate cycle is oxygen dependent but does not use O2. The CAC depends on NADH and FADH to be oxidized and regenerated. However, they cannot be oxidized without the use of O2 at the final electron acceptor within the ETC

(T/F) Increasing the concentration of one intermediate within the CAC does not effect the following intermediate concentrations

False — increasing the concentration of one intermediate increases the concentrations of all 8 intermediates

Explain how the final step of the CAC is energetically possible

Since step 1 of the CAC is highly exergonic and the CAC is a cycle. This allows for the highly endergonic, step 8 to push forward

Which of the following statements regarding the citrate cycle are TRUE?  

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a) There is net synthesis of intermediate molecules such as citrate.

b) The first step of the pathway requires two substrates: acetyl CoA and citrate.

c) The pathway is  O₂ dependent and use O₂ to regenerate electron carriers.

d) If pathway intermediates are siphoned off and used for other pathways  the cycle can not continue running. 

e) There are 10 steps - two of which are decarboxylation reactions.

d) If pathway intermediates are siphoned off and used for other pathways  the cycle can not continue running. 

For each acetyl CoA that enters the Citrate Cycle, ______ pairs of electrons are captured _____ NADH is/are generated _____ FADH₂ is/are generated _____ GTP/ATP is/are produced by substrate-level phosphorylation

4; 3; 1 ;1

What is step 1 of the CAC

Citrate synthase catalyzes the irreversible condensation of acetyl-CoA with Oxaloacetate

What is step 2 of the CAC

Aconitase catalyzes the reversible isomerization of citrate to isocitrate

What is step 3 of the CAC

NAD+ dependent isocitrate dehydrogenase catalyzes te first oxidative decarboxylation

What is step 4 of the CAC

a-ketoglutarate dehydrogenase catalyzes the second oxidative decarboxylation

What is step 5 of the CAC

Succinyl CoA synthetase catalyzes substrate level phosphorylation to produce GTP or ATP

Which step is a condensation reaction? 

1

Describe the condensation reaction in the citric acid cycle, specifying the number of carbons in the molecules involved.

During step 1, the acetyl group of acetyl-CoA (a 2-carbon unit) condenses with oxaloacetate (a 4-carbon molecule) to form a new carbon-carbon bond. This first produces an intermediate called citryl-CoA (still attached to Coenzyme A).
Citryl-CoA is then hydrolyzed, releasing free CoA-SH and yielding citrate, a 6-carbon molecule

What type of reaction does Aconitase catalyze?

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a) reduction

b) condensation

c) isomerization

d) decarboxylation

e) phosphorylation

c) isomerization

Which steps release carbon dioxide? Select all that apply.

Steps 3 and 4

Which step is catalyzed by an enzyme that uses TPP as a prosthetic group?

4

Which step generates ATP or GTP?

5

Which step uses Coenzyme A as a cosubstrate?

4

What is citrate synthase regulated by

Inhibition: Succinyl-CoA, Citrate, NADH, & ATP

Activation: ADP

What is isocitrate dehydrogenase regulated by

Inhibition: ATP

Activation: Ca²⁺ & ADP

What is a-ketoglutarate dehydrogenase complex regulated by

Inhibition: Succinyl-CoA & NADH

Activation: Ca²⁺

The citrate cycle is primarily regulated at ____ allosteric enzymes

3

Which steps are catalyzed by regulatory enzymes?

1, 3, & 4

A high concentration of which molecule would inhibit citrate synthase in the citrate cycle?

a) AMP

b) ADP

c) NAD+

d) ATP

d) ATP

Which steps are activated by increased intracellular Calcium?

Steps 3 & 4

The type of inhibition where citrate inhibits citrate synthase and PFK-1 is called _________ inhibition

Feedback

What are the final products of the CAC

2 CO₂, 4 pairs of e-, 3 NADH and 1 FADH , 1 GTP/ATP made

A pathway that serves in both anabolic and catabolic processes is called a(n) _______ pathway

amphibolic

What is the role of pyruvate carboxylase?

a) It converts amino acids into oxaloacetate.

b) It generates acetyl-coA from pyruvate.

c) It converts succinyl-CoA into heme.

d) It generates oxaloacetate from pyruvate.

e) It converts the amino acid glutamate into α-ketoglutarate

d) It generates oxaloacetate from pyruvate.

Identify the specific term that describes the type of reactions catalyzed by pyruvate carboxylase.
________________ reaction

anaplerotic

Define an anaplerotic reaction

An anaplerotic reaction is a reaction that replenishes the intermediates of a metabolic cycle — specifically, in this context, the intermediates of the citric acid cycle (CAC).

What molecules is citrate used to make

fatty acids & sterols

What molecules is a-ketoglutarate used to make

Directly: Glutamate

Indirectly: purines, glutamine, proline, arginine

What molecules is Succinyl-CoA used to make

porphyrins, heme

What molecules is oxaloacetate used to make

Directly: Aspartate, asparagine,

Indirectly: pyrimidines

Directly: phosphoenolpyruvate

Indirectly: glucose, serine, glycine, cysteine, phenylalanine, tyrosine, tryptophan

What is the role of malic enzyme

to covert pyruvate to malate

What is the role of PEP carboxylase

To convert PEP to Oxaloacetate

What is the role of PEP carboxykinase

To convert Oxaloacetate to PEP

What is the role of pyruvate carboxylase

To convert pyruvate to oxaloacetate